Researcher Discusses Fatigue and PBC

We sat down with Dr. Marina Silveira to learn more about her research on primary biliary cholangitis (PBC). Dr. Silveira is a recipient of ALF’s 2018 PBC Fund for the Cure Award.  The American Liver Foundation is encouraged by her work and we hope that you will be, too.

As always, we would like to remind readers that this blog is designed to increase general knowledge only and is not a substitute for professional medical advice, diagnosis or treatment for specific conditions.

What is your first memory/experience of wanting to be involved in scientific research?

My first memory of wanting to be involved in scientific research is closely related to my first memory of wanting to pursue medical training. I realized there were many unanswered questions in medicine and the only way to truly help many people was to search for answers in a methodical way.

How did you learn that you had won an ALF Research Award?

From an early morning email from the ALF, which was a very special way to start the day! I am very grateful to the ALF for the opportunity to help patients with PBC suffering from fatigue.

Describe your Research Award Project in very simple (layman’s) language?

Fatigue is a common symptom in patients with primary biliary cholangitis, which can lead to poor quality of life and does not have any effective treatment. For my project, twenty eligible patients with moderate to severe fatigue who are currently on stable therapy with ursodiol for at least 6 months will be enrolled into a clinical trial in which their fatigue and other symptoms will be monitored closely over the course of almost one year. After at least eight weeks of observation, patients will complete an eight-week mindfulness-based intervention program (once a week for at least 2.5 hours) aimed at improving the symptoms of fatigue in patients with PBC. Patients will be followed up to a total of one year so that blood tests, physical activity, and symptoms including fatigue can be measured at different times to look for changes before and after the mindfulness-based intervention program.

Are there other studies that suggest mindfulness can help address symptoms of fatigue in people with PBC or other chronic conditions?

There are many studies that have evaluated the use of mindfulness-based intervention in chronic diseases associated with fatigue, including multiple sclerosis and cancer. They have shown that mindfulness can result in improvement of fatigue and quality of life. However, there have been very few studies of mindfulness interventions in chronic liver diseases, and none that have been published in patients with PBC.

We recently completed, in collaboration with the Yale Stress Center at Yale School of Medicine, a study of mindfulness-based stress reduction in patients with autoimmune hepatitis, which is another rare chronic liver condition. Because the final results are not available right now (some patients are still completing the follow-up tests), I can only share preliminary results that showed the mindfulness-based program led to improvement of stress and liver-related inflammation. These preliminary results will be presented at the AASLD Liver Meeting in November 2018.

Will you be collaborating again with the Yale Stress Center?

We are very grateful to be able to work with them again.  The experiences of many patients who have gone through mindfulness-based programs at the Yale Stress Center have been incredible. We received overwhelmingly positive feedback from patients in our prior study who really enjoyed the whole process and said they would do it again in a heartbeat.

In this prior study, the Yale Center offered the practice of mindfulness as a group program, though no medical information needed to be shared.  As a result, participants had the opportunity to interact with other patients with the same liver disease.  Through shared experiences and challenges, participants developed bonds that have gone beyond the mindfulness-based intervention program.

It is worth noting that the PBC study will be somewhat different. It will focus on fatigue and not stress alone.

What outcomes are of interest to you?

In addition to studying whether mindfulness-based interventions work for the treatment of fatigue in people living with PBC, we also would like to see if the effect is long-lasting. That is why we want to follow patients beyond the completion of the eight-week program. We are still deciding whether we will utilize a home tool to guide self-practice of mindfulness for some patients. Doing so might help us to understand if activities beyond the group intervention can help extend the results of the program. If we cannot practically do this during this study, it will certainly be part of our next larger study!

Are you considering additional PBC studies?

I hope that this study helps us design larger studies to further understand why some patients with PBC develop fatigue, how their bodies and minds are affected by fatigue, and whether there are treatments that can result in a cure of the fatigue and an improvement in the quality of life of those affected by this disease

When you discover more about PBC-related fatigue, we would love to hear your findings. What is currently known?

Chronic fatigue is the most common symptom that patients with primary biliary cholangitis will experience throughout the course of their disease. Fatigue is not related to disease activity or the stage of disease and tends to wax and wane throughout the course of illness. In many cases, PBC can be managed with ursodiol.  Many other promising drugs are also being studied. However, ursodiol does not improve fatigue and, so far, no medications have been shown to reliably improve fatigue.

Why do you think that medications the help PBC-related fatigue don’t exist?

This is probably in part because fatigue is so complex, and we don’t know exactly what leads to its development. Many factors are likely involved, such as changes to the central nervous system, the autonomic nervous system, and the muscle metabolism. Many changes that are related to fatigue can be observed in patients with PBC, including memory changes, difficulty concentrating, sleep disturbances, mood changes, and impaired physical activity. Because fatigue can limit a person’s ability to work and perform their daily activities, and affects their mood and quality of life, treatment of fatigue is identified as a priority for research for patients with PBC. We need to continue to study new strategies to help address the debilitating symptoms that can accompany the disease – which is where this study comes in.

Do you have any fatigue management tips for the readers?

Fatigue can be extremely difficult to deal with and, unfortunately, there is no currently available treatment. One of the most important tips I recommend to patients for managing PBC-related fatigue is to learn more about your liver disease and its symptoms. Educating your loved ones on your symptoms and how they impact you on a daily basis may be helpful as well. A supportive environment can improve your sense of wellbeing and may help you develop modifications to accommodate the burden of fatigue.

Trying to engage in regular social activities and some degree of physical activity are other helpful strategies, as difficult as that may be when you are living with fatigue. Remember to always consult with your physician about what type of physical activity is adequate for your unique condition.

Beyond lifestyles changes are their other actions those with PBC can take?

Any other treatable conditions that may contribute to fatigue should be addressed, including itchiness, thyroid problems, anemia, vitamin D deficiency, sleep apnea or other sleep disturbances, depression, and use of certain medications.

Finally, an important tip for dealing with fatigue and PBC in general is finding a physician that is familiar with your medical condition and can work with you on your symptoms and some of the strategies to improve them.

What do you want individuals with PBC to know about living with their condition?

Despite all of the advances in the diagnosis and treatment of PBC, there is still no cure for the disease. Living with PBC can be extremely challenging and many patients feel powerless and alone. Every patient with PBC should know that they are not alone.  They inspire many physicians and scientists to study PBC and its complications, with the common goal of finding a cure and improving the lives of those affected by this disease. We need to work together to get to our common goal. I am so grateful to the ALF for the opportunity granted to me by this award.